In many cancers, microRNA-193a (miR-193a) is a suppressor miRNA, but its underlying anti-oncogenic activity in breast cancer is not known. In this study, we found decreased miR-193a (specifically, miR-193a-5p) expression not only in breast cancer cell lines but also in breast cancer tissues as compared with the adjacent non-tumor tissues. Ectopic miR-193a overexpression inhibited the proliferation, colony formation, migration, and invasion of MDA-MB-231 and BT549 cells. miR-193a reduced Wilms’ tumor 1 (WT1) expression and repressed luciferase reporter activity by binding WT1 coding region sequences; mutation of the predicted miR-193a binding site abolished this effect. miR-193a and WT1 expression were significantly inversely correlated in breast cancer tissues. Importantly, the anti-cancer activity induced by miR-193a was partially reversed by WT1 overexpression, indicating an important role for WT1 in such activity related to miR-193a. Our results reveal that miR-193a-WT1 interaction plays an important role in breast cancer metastasis, and suggest that restoring miR-193a expression is a therapeutic strategy in breast cancer.

KLF11 (Krüppel-like factor 11) belongs to the family of Sp1/Krüppel-like zinc finger transcription factors that play important roles in a variety of cell types and tissues. KLF11 was initially described as a transforming growth factor-beta (TGF-β) inducible immediate early gene (TIEG). KLF11 promotes the effects of TGF-β on cell growth control by influencing the TGFβ–Smads signaling pathway and regulating the transcription of genes that induce either apoptosis or cell cycle arrest. In carcinogenesis, KLF11 can show diverse effects. Its function as a tumor suppressor gene can be suppressed by phosphorylation of its binding domains via oncogenic pathways. However, KLF 11 can itself also show tumor-promoting effects and seems to have a crucial role in the epithelial–mesenchymal transition process. Here, we review the current knowledge about the function of KLF11 in cell growth regulation. We focus on its transcriptional regulatory function and its influence on the TGF-β signaling pathway. We further discuss its possible role in mediating crosstalk between various signaling pathways in normal cell growth and in carcinogenesis.

Synchronous multiple primary malignant tumors (MPMTs) are rare in young adults. Genomic profiling of synchronous MPMTs has not been systematically investigated to elucidate their genetic associations, but may be important to assist diagnosis and guide appropriate treatment strategy. In the present study, mutation profiling was performed using targeted next generation sequencing (NGS) on 416 cancer‑related genes in synchronous triple primary tumors of the lung, kidney and thyroid in a 32‑year‑old female patient. The patient was diagnosed with moderately differentiated lung adenocarcinoma (T2aN0M0; stage IB), renal clear cell carcinoma (T1aN0M0; stage I), and thyroid papillary carcinoma (T1N1aM0, stage III) by pathological assessments. Clinically actionable mutations in EGFR and BRAF genes were identified in the lung and the thyroid lesions, respectively. Three tumors demonstrated distinct genomic profiles, suggesting that all tumors were independent primary tumors, which was consistent with histopathological assessment. Three potential germline cancer susceptibility mutations were shared between this patient and her father who was diagnosed with lung cancer. The present results demonstrated that, in the context of identical germline background and environmental exposure, multiple synchronous tumors in the same patient may have distinct mutation profiles and can be driven by distinct molecular events. Combination therapies may need to be considered during treatment decision‑making.

Background: An abundance of tumor-associated macrophages has been shown to be an independent prognostic factor for a poor prognosis of human breast cancer (BC). Adipose tissue accounts for the largest proportion of the breast and has also been identified as an independent indicator of poor survival in BC. This study aims to elucidate if the influence of adipose tissue in BC might be mediated by macrophages. The roles of macrophages in the breast tumor-stroma (breast tumor stroma macrophages, BTSM) and macrophages in the surrounding adipose tissue (breast adipose tissue macrophages, BATM) were explored separately. Methods: Two hundred ninety-eight BC tissue samples were analyzed immunohistochemically. The number of macrophages was detected by CD68+ staining. The quantity of BATMs and BTSMs was correlated to clinical and pathological parameters as well as to disease-free survival (DFS) and overall survival (OS). Results: The amounts of BATMs and BTSMs strongly correlated with each other (r = 0.5, p = 2.98E−15). The quantity of BTSMs, but not of BATMs, was significantly associated with the BC molecular subtype (p = 0.000011), and all triple-negative BC tumors contained high amounts of BTSMs. BATMs were negatively associated with DFS (p = 0.0332). Both BATMs (p = 0.000401) and BTSMs (p = 0.021) were negatively associated with OS in the Kaplan-Meier analysis, but only BATMs remained an independent factor in the multivariate Cox-regression analysis (HR = 4.464, p = 0.004). Combining prostaglandin E2 receptor 3 (EP3)-expression and the quantity of BATMs, a subgroup with an extremely poor prognosis could be identified (median OS 2.31 years in the “high BATMs/low EP3” subgroup compared to 11.42 years in the most favorable “low BATMs/high EP3” subgroup, p = 0.000002). Conclusion: Our findings suggest that BTSMs and BATMs seem to be involved differently in BC. Breast adipose tissue might contribute to the aggressiveness of BC via BATMs, which were independently associated with BC survival. BATMs’ role and occurrence might be functionally dependent on EP3, as a combination of both factors was strongly associated with survival. Targeting BATMs—eventually in combination with targeting the EP3-pathway—might be promising for future therapies.